The prostaglandins are C-20 unsaturated fatty acids which exhibit diverse physiological effects. Their structure, nomenclature, biological activities and medicinal use have been described in U.S. Pat. Nos. 3,971,825 and 3,984,400.
A common problem confronting medical scientists who attempt to make biologically efficacious, synthetic drugs is modulation of the biological action of an appropriate lead compound. A traditional approach seeks an increase in biological potency. The prostaglandin approach, however, is framed around increased oral activity and increased duration of action. In addition, enhancement of one of the diverse physiological effects of the prostaglandin class and diminution of the others are sought so that the synthetic prostaglandins will not exhibit incompatible side effects. For example, it would be clinically inadvisable to administer an antiulcer synthetic prostaglandin that also causes diarrhea.
To achieve increased selectivity, efforts have focused on the "active" sites of the natural prostaglandins. In the main, these include the C-1 carboxylic acid group, the cyclopentane ring and the lipophilic end of the bottom side chain. Such work is publicized in the following patents and articles: U.S. Pat. Nos. 4,024,179; 3,954,741; 3,987,087; 3,932,389; 3,054,741; Netherlands Octrooaanvrage No. 7,306,030; G. Traverso et. al., Il. Farmaco Ed. Sci. 28, 1040 (1973); C. H. Lin et. al., Syn. Com. 6(7)503 (1976); and H. Wakatsuka, Prostaglandins, 8, 341 (1974).